Hypoxia is one of the important features of tumor microenvironment, and it is mainly caused by the imbalance between oxygen supply and oxygen consumption of tumor tissues. Hypoxia has an extremely important effect on tumor growth and metastasis, such as triggering drug resistance and radiation resistance, so it has always been regarded as a major obstacle to tumor treatment. Meanwhile, hypoxic microenvironment is becoming a favorable target for tumor therapy because of its uniqueness in tumor site. Nanotechnology has high targeting ability and good histocompatibility, and has been widely applied in tumor therapy. This review summarizes recent advances in new nano-delivery systems based on hypoxic microenvironment in tumor chemotherapy, radiotherapy, photodynamic therapy and immunotherapy.